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PLoS One. 2009 Dec 30;4(12):e8496. doi: 10.1371/journal.pone.0008496.

Cholesterol homeostasis in two commonly used human prostate cancer cell-lines, LNCaP and PC-3.

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  • 1School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.

Abstract

BACKGROUND:

Recently, there has been renewed interest in the link between cholesterol and prostate cancer. It has been previously reported that in vitro, prostate cancer cells lack sterol-mediated feedback regulation of the major transcription factor in cholesterol homeostasis, sterol-regulatory element binding protein 2 (SREBP-2). This could explain the accumulation of cholesterol observed in clinical prostate cancers. Consequently, perturbed feedback regulation to increased sterol levels has become a pervasive concept in the prostate cancer setting. Here, we aimed to explore this in greater depth.

METHODOLOGY/PRINCIPAL FINDINGS:

After altering the cellular cholesterol status in LNCaP and PC-3 prostate cancer cells, we examined SREBP-2 processing, downstream effects on promoter activity and expression of SREBP-2 target genes, and functional activity (low-density lipoprotein uptake, cholesterol synthesis). In doing so, we observed that LNCaP and PC-3 cells were sensitive to increased sterol levels. In contrast, lowering cholesterol levels via statin treatment generated a greater response in LNCaP cells than PC-3 cells. This highlighted an important difference between these cell-lines: basal SREBP-2 activity appeared to be higher in PC-3 cells, reducing sensitivity to decreased cholesterol levels.

CONCLUSION/SIGNIFICANCE:

Thus, prostate cancer cells are sensitive to changing sterol levels in vitro, but the extent of this regulation differs between prostate cancer cell-lines. These results shed new light on the regulation of cholesterol metabolism in two commonly used prostate cancer cell-lines, and emphasize the importance of establishing whether or not cholesterol homeostasis is perturbed in prostate cancer in vivo.

PMID:
20041144
[PubMed - indexed for MEDLINE]
PMCID:
PMC2794383
Free PMC Article

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